Squeeze flow and compaction behavior of toughened polyimide matrix composites

The main emphasis was placed upon the squeeze flow and compaction behavior of the Lewis Research Center (LaRC) research project series polyimide matrix composites. The measurement of squeeze film flow behavior was performed by a plastometer which monitors the change of thickness of a prepreg specimen laid between two parallel plates under the specified temperature and pressure history. A critical evaluation of the plastometer data was attempted by examining the morphology of the specimen at various points during the squeeze flow. The effects of crosslinks (Mc) of resin, imidization (B-ataging) condition, and pressure on the squeeze flow behavior were examined. Results are given

Tumor microenvironment: becoming sick of Myc

Several years ago, we described Myc as “the oncogene from hell”, since evidence had just emerged that Myc, aside from being responsible for cell-cycle progression and tumor expansion, was also able to induce genomic instability in culture, wreaking havoc in tumor cells and accelerating tumor progression (Soucek and Evan, Cancer Cell 1:406–408, 2002; Vafa et al., Mol Cell 9:1031–1044, 2002). In this review, we discuss recent publications that expand Myc’s evil armory to include coordination of the crosstalk between tumor and microenvironment. Indeed, endogenous Myc, acting as a client for upstream oncogenic lesions, instructs the tumor stroma, engages a complex inflammatory response and induces angiogenesis, thus allowing the tumor to thrive. This is highly topical in light of the fact that Hanahan and Weinberg have recently redefined the hallmarks of cancer and pointed out that genomic instability and inflammation are essential for both their acquisition and development (Hanahan and Weinberg, Cell 144:646–674, 2011). Myc, it seems, is behind it all

The long journey to bring a Myc inhibitor to the clinic

Whitfield and Soucek discuss decades of research and a vast array of strategies that are finally yielding clinical trials for Myc inhibitors in cancer. The oncogene Myc is deregulated in the majority of human tumors and drives numerous hallmarks of cancer. Despite its indisputable role in cancer development and maintenance, Myc is still undrugged. Developing a clinical inhibitor for Myc has been particularly challenging owing to its intrinsically disordered nature and lack of a binding pocket, coupled with concerns regarding potentially deleterious side effects in normal proliferating tissues. However, major breakthroughs in the development of Myc inhibitors have arisen in the last couple of years. Notably, the direct Myc inhibitor that we developed has just entered clinical trials. Celebrating this milestone, with this Perspective, we pay homage to the different strategies developed so far against Myc and all of the researchers focused on developing treatments for a target long deemed undruggable

Alternativity and reciprocity in the Cayley-Dickson algebra

We calculate the eigenvalue \rho of the multiplication mapping R on the Cayley-Dickson algebra A_n. If the element in A_n is composed of a pair of alternative elements in A_{n-1}, half the eigenvectors of R in A_n are still eigenvectors in the subspace which is isomorphic to A_{n-1}. The invariant under the reciprocal transformation A_n \times A_{n} \ni (x,y) -> (-y,x) plays a fundamental role in simplifying the functional form of \rho. If some physical field can be identified with the eigenspace of R, with an injective map from the field to a scalar quantity (such as a mass) m, then there is a one-to-one map \pi: m \mapsto \rho. As an example, the electro-weak gauge field can be regarded as the eigenspace of R, where \pi implies that the W-boson mass is less than the Z-boson mass, as in the standard model.Comment: To be published in J. Phys. A: Mathematical and Genera

Strategies to Inhibit Myc and Their Clinical Applicability

Myc is an oncogene deregulated in most-perhaps all-human cancers. Each Myc family member, c-, L-, and N-Myc, has been connected to tumor progression and maintenance. Myc is recognized as a "most wanted" target for cancer therapy, but has for many years been considered undruggable, mainly due to its nuclear localization, lack of a defined ligand binding site, and physiological function essential to the maintenance of normal tissues. The challenge of identifying a pharmacophore capable of overcoming these hurdles is reflected in the current absence of a clinically-viable Myc inhibitor. The first attempts to inhibit Myc used antisense technology some three decades ago, followed by small molecule inhibitors discovered through "classical" compound library screens. Notable breakthroughs proving the feasibility of systemic Myc inhibition were made with the Myc dominant negative mutant Omomyc, showing both the great promise in targeting this infamous oncogene for cancer treatment as well as allaying fears about the deleterious side effects that Myc inhibition might have on normal proliferating tissues. During this time many other strategies have appeared in an attempt to drug the undruggable, including direct and indirect targeting, knockdown, protein/protein and DNA interaction inhibitors, and translation and expression regulation. The inhibitors range from traditional small molecules to natural chemicals, to RNA and antisense, to peptides and miniproteins. Here, we briefly describe the many approaches taken so far, with a particular focus on their potential clinical applicability